Synthesis of Asthma Drug Zafirlukast (Accolate) Using Intramolecular Oxidative Coupling via sp(3) C-H Bond Activation

利用sp(3) CH键活化进行分子内氧化偶联合成哮喘药物扎鲁司特(Accolate)

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Abstract

The FDA-approved drug for the treatment of asthma, zafirlukast, is synthesized engaging multiple catalytic reactions including a new method for the construction of 3-aroylindoles via oxidative cyclization. The highlights include transition-metal and peroxide free C-H bond activation using the stoichiometric amount of sodium persulfate as an oxidizing agent in the construction of 3-aroylindole, avoiding transition metal, with over 28% overall yield. The complete process has a turnaround time of 28 h to get the target molecule starting from substituted aniline, with practically no protecting groups.

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